Physiological Metrics as Candidate Predictors of Antibody Response Following Vaccination Against Covid-19

Abstract

Methods, systems, and devices are provided for predicting the robustness of an antibody response of a subject to the SARS-COV-2 spike protein receptor binding domain based on measurement of physiological metrics following vaccination. In particular, one or more physiological metrics of the subject selected from dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration are measured with a wearable device before and after vaccinating the subject, wherein increases in dermal temperature deviation, heart rate, and respiratory rate, and decreases in heart rate variability on the first night after administration of the vaccine to the subject are correlated with greater antibody responses to the SARS-COV-2 spike protein.

1 . A method of determining whether vaccination of a subject against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) produces an antibody response to a spike protein receptor binding domain (RBD) of the SARS-COV-2, the method comprising:
 vaccinating the subject by administering a vaccine against the SARS-COV-2; and   measuring one or more physiological metrics of the subject selected from dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration before and after said vaccinating the subject using a measuring device, wherein increases in the dermal temperature deviation, heart rate, and respiratory rate, and decreases in the heart rate variability and deep sleep duration on the first night after said vaccinating the subject compared to a pre-vaccination dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration of the subject correlate with increases in the antibody response of the subject to the SARS-COV-2 spike protein.   
     
     
         2 . The method of  claim 1 , wherein the vaccine comprises mRNA or DNA encoding the SARS-COV-2 spike protein RBD. 
     
     
         3 . The method of  claim 1 , wherein the measuring comprises measuring two or more of the physiological metrics. 
     
     
         4 . The method of  claim 3 , wherein the measuring comprises measuring dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein said vaccinating comprises administering at least a first dose of the vaccine and a second dose of the vaccine to the subject, wherein said measuring comprises measuring the one or more physiological metrics of the subject before and after the second dose of the vaccine is administered to the subject. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 6 , wherein said vaccinating comprises administering the vaccine according to a prime-boost regimen. 
     
     
         9 . The method of  claim 8 , wherein said vaccinating comprises administering one or more booster doses of the vaccine to the subject. 
     
     
         10 . The method of  claim 9 , wherein said measuring comprises measuring the one or more physiological metrics of the subject before and after a booster dose of the vaccine is administered to the subject. 
     
     
         11 . The method of  claim 1 , wherein the measuring device is a portable device or a wearable device worn by the subject. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the measuring device comprises a tri-axial accelerometer. 
     
     
         14 . The method of  claim 1 , wherein the heart rate, respiratory rate, and heart rate variability are measured from a photoplethysmogram (PPG) signal, and wherein the dermal temperature is measured using a negative temperature coefficient (NTC) thermistor. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the increases in the dermal temperature deviation, heart rate, and respiratory rate, and decreases in the heart rate variability and deep sleep duration on the first night following said vaccinating the subject are correlated with increases in the antibody response to the SARS-CoV-2 spike protein using a Spearman rank-order correlation analysis or a Kendall rank order correlation analysis. 
     
     
         18 . The method of  claim 1 , wherein the physiological metrics are measured during sleep periods, wake periods, or both sleep and wake periods of the subject. 
     
     
         19 . The method of  claim 1 , further comprising measuring the one or more physiological metrics of the subject for at least one or two months prior to vaccination of the subject to determine average baseline values for the one or more physiological metrics, wherein increases in dermal temperature deviation, heart rate, and respiratory rate, and decreases in heart rate variability and deep sleep duration on the first night after said vaccinating the subject compared to the average baseline values for the dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration are correlated with increases in the antibody response of the subject to the SARS-CoV-2 spike protein. 
     
     
         20 . The method of  claim 19 , further comprising measuring average overnight dermal temperature of the subject for at least one or two months prior to vaccination of the subject to determine an average baseline value for the overnight dermal temperature, wherein the temperature deviation is computed as a difference between an average overnight temperature of the subject and the average baseline value of the overnight temperature; and/or
 further comprising measuring a serum level of antibodies to the SARS-COV-2 spike protein RBD for the subject if the dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration on the first night after said vaccinating the subject indicate that the level of antibodies to the SARS-COV-2 spike protein RBD is below a threshold level for effective neutralization of SARS-COV-2.   
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , further comprising administering another booster dose of the vaccine to the subject if the one or more physiological metrics of the subject indicate that the level of antibodies to the SARS-COV-2 spike protein RBD is below a threshold level for effective neutralization of SARS-COV-2. 
     
     
         23 . A system for determining whether vaccination of a subject against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) produces an antibody response to a spike protein receptor binding domain (RBD) of the SARS-COV-2, the system comprising:
 a) a measuring device configured to measure one or more physiological metrics of the subject selected from dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration before and after vaccinating the subject against SARS-COV-2;   b) a processor programmed to analyze the physiological metrics using one or more algorithms to correlate increases in the dermal temperature deviation, heart rate, and respiratory rate, and decreases in the heart rate variability and deep sleep duration on the first night after said vaccinating the subject compared to a pre-vaccination dermal temperature deviation, heart rate, respiratory rate, heart rate variability, and deep sleep duration with increases in the antibody response of the subject to the SARS-COV-2 spike protein RBD; and   c) an output device configured to display information regarding the antibody response of the subject to the SARS-COV-2 spike protein RBD.   
     
     
         24 . The system of  claim 23 , further comprising a storage component operably coupled to the measuring device and the processor, wherein the storage component is configured to record physiological metric data measured by the measuring device. 
     
     
         25 . The system of  claim 23 , wherein the one or more algorithms are selected from a Spearman rank-order correlation analysis and a Kendall rank order correlation analysis. 
     
     
         26 . The system of  claim 23 , wherein the measuring device comprises a negative temperature coefficient (NTC) thermistor or a tri-axial accelerometer. 
     
     
         27 . (canceled) 
     
     
         28 . The system of  claim 23 , wherein the measuring device measures heart rate, respiratory rate, and heart rate variability from a photoplethysmogram (PPG) signal. 
     
     
         29 . The system of  claim 23 , wherein the measuring device is a portable device or a wearable device worn by the subject. 
     
     
         30 . (canceled) 
     
     
         31 . A kit comprising the system of  claim 23 , packaging for the system, and instructions for using the system for determining whether vaccination of a subject against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) produces an antibody response to a spike protein receptor binding domain (RBD) of the SARS-COV-2.